The objectives of the proposed program are to carry out clinical pharmacokinetic and biopharmaceutic studies to increase the safety and efficacy of drug therapy in man. A Clinical Pharmacokinetics Laboratory at a major general hospital under the direction of a qualified clinical pharmacokineticist--supported by a panel of specialists in pharmacokinetics drug analysis, clinical pharmacology, and by an already operative, fully staffed drug information center--will develop individualized dosage regimens for such drugs as digoxin, diphenylhydantoin, quinidine, theophylline, gentamycin and several other antibiotics based on physiologic and pharmacokinetic parameters, and will explore pharmacokinetic aspects of unusual drug responses and special problems such as drug dosage regimens for patients undergoing hemodialysis. These regimens will be refined and adjusted on the basis of regular monitoring of plasma concentrations and (where feasible) response. The clinical research will be interdigitated with a comprehensive program focusing on basic pharmacokinetics research on drug bioavailability, time course of reversible pharmacologic effects, and development of physiologically realistic biomathematical models. Bibliographic references: Kinetics of Pharmacologic Effect: Shen, D., O'Malley, K. and Gibaldi, M., Pharmacodynamics of minoxidil as a guide for individualizing dosage regimens in hypertension, Clin. Pharmacol. Therap. 17: 593-598 (1975). Jusko, W.J., Slaunwhite, W.R., Jr., and Aceto, T., Jr., Partial pharmacodynamic model for the circadian- episodic secretion of cortisol in man, J. Clin. Endocrinol. Metab. 40:278-289 (1975).